The use of protamine sulfate is the only commercially available choice that clinicians have to counteract the anticoagulant effect of heparin. While the incidence of any one type of adverse response is generally small the sheer number of different adverse reactions translates into a significant percentage, as high as 27%. The number of patients experiencing adverse reactions associated with heparin reversal ranges from approximately 10,500 to 70,000 open heart patients per year just in the U.S. The need for an alternative means of heparin reversal which obviates the need for protamine sulfate is well recognized. It is the overall goal of the proposed work to develop a device that will reverse the anticoagulant effect of heparin at the end of cardiopulmonary bypass and do it in a safe, cost-effective, and predictable manner. The proposed heparin removal device combines two commercially available technologies to achieve a high capacity, low priming volume system that utilizes high affinity derivatized agarose to remove heparin. One novel feature of the device is that whole blood does not have to come into direct contact with the derivatized agarose. Phase I work will optimize the chemistry involved in derivatizing the high affinity agarose beads and will evaluate several approaches to dry the derivatized beads without compromising heparin-binding activity. In addition, an effort will be made to identify plasma proteins adsorbing to the beads using two-dimensional electrophoresis. By the end of Phase I a prototype device will be constructed to test this unique heparin reversal system in animals and humans during Phase II studies. Preliminary in vitro experiments indicate that a heparin clearance of 85-90 ml/min can be achieved with a less than optimal device. Roughly, one gram of wet derivatized beads can adsorb 1000 units of heparin in 15 minutes.